Background Ferroptosis is an iron‐dependent and oxidative cell death form. Recent studies suggested that circular RNAs (circRNAs) regulated ferroptosis in tumour cells. Circ_0007142 was identified as a carcinogenic molecule in colorectal cancer (CRC), but its function on ferroptosis in CRC remains unknown. Methods Circ_0007142, microRNA‐874‐3p (miR‐874‐3p) and glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) levels were assayed using the quantitative real‐time polymerase chain reaction (qRT‐PCR). Cell survival and proliferation were measured by Cell Counting Kit‐8 (CCK‐8) assay. Protein detection was performed by Western blot. Cell apoptosis was analysed by flow cytometry. Ferroptosis was assessed by iron accumulation and oxidative stress. Target binding was evaluated by dual‐luciferase reporter assay. In vivo research was conducted by tumour xenograft in mice. Results Circ_0007142 was overexpressed in CRC. After expression inhibition of circ_0007142, proliferation was reduced, while apoptosis and ferroptosis were facilitated in CRC cells. Mechanically, circ_0007142 was found as a miR‐874‐3p sponge and miR‐874‐3p inhibitor eliminated the regulation of si‐circ_0007142 in CRC cells. MiR‐874‐3p targeted GDPD5 and upregulation of GDPD5 reversed the miR‐874‐3p‐triggered tumour inhibition and ferroptosis promotion in CRC cells. Moreover, GDPD5 was regulated by the circ_0007142/miR‐874‐3p axis. Circ_0007142 also affected CRC tumorigenesis in vivo through the regulation of miR‐874‐3p and GDPD5. Conclusion All these findings proved that circ_0007142/miR‐874‐3p/GDPD5 axis regulated tumorigenesis and ferroptosis of CRC cells. Circ_0007142 might be an available marker for ferroptosis in CRC therapy.
Background: The FOS gene is located on human chromosome 14q21–31 and encodes the nuclear oncoprotein c-Fos. This study analyzed the correlation between the FOS noncoding region rs7101 and rs1063169 polymorphisms and colorectal cancer susceptibility and prognosis. Methods: We analyzed the FOS genotypes in 432 colorectal cancer patients and 315 healthy subjects by PCR/Sanger sequencing. Survival was analyzed by Kaplan–Meier and Cox regression analysis. Western blot was used to detect the expression of c-Fos protein in cancer tissues and adjacent tissues in colorectal cancer patients with different genotypes. Results: The presence of a T allele at rs7101 and a T allele at rs1063169 in FOS carried a higher risk of colorectal cancer [adjusted odds ratio (OR) = 1.237, 95% confidence interval (95% CI) = 1.131–1.346, P ≤ .001 and adjusted OR = 1.218, 95% CI = 1.111–1.327, P ≤ .001, respectively]. c-Fos protein levels were significantly higher in variant cancer tissues than in normal mucosa tissues ( P < .05), and c-Fos proteins levels were also higher in homozygous variant cancer tissues than in heterozygous variant cancer tissues. The 3-year survival rate of patients with wild-type FOS was higher than that of patients with variant FOS ( P < .05). Conclusion: The rs7101 and rs1063169 polymorphisms in the noncoding region of FOS are associated with the risk of developing colorectal cancer and the progression of colorectal cancer, which may be because the mutation enhances the expression of c-Fos protein to promote the incidence and development of colorectal cancer.
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